Lead (Pb) causes nephropathy and hypertension at high body burdens. Blood lead (BPb) concentrations less than 40 ug/dL due to unusual environmental exposure have been considered non- toxic, but clinical experiments indicate Pb may paly a role in the development of renal dysfunction in hypertensive individuals. Our goals are to confirm, expand and delineate these relationships. To accomplish this, subjects with hypertension who subsequently developed nephropathy will be chelated with CaNa2EDTA in a standardized protocol used in previous experiments to estimate body burdens of Pb. These subjects will be compared to controls with renal disease of known cause who have secondary hypertension. Neither group will have past unusual exposure to Pb and will otherwise be similar for BPb and free erythrocyte protoporphyrins. If greater Pb is excreted in the hypertensive nephropathy group, this will support the hypothesis concerning Pb's role. A second study of similar hypertensive nephropathy subjects will evaluate treatment with an oral, efficacious, non- toxic Pb chelator, dimercaptosuccinic acid (DMSA). If improvements in renal function or blood pressure occur with increased urinary excretion of Pb, then the role of Pb will be substantiated in this pathology. Also, bone activity may effect the chelatability of Pb. Hyperparathyroid subjects will be chelated with CaNa2EDTA. Urinary Pb excretion may be higher in these subjects before parathyroidectomy as compared to afterwards. Bone activity may determine how quickly Pb reequilibrates after chelation. Therefore, during this study multiple BPb determinations will allow determination of reequilibration kinetics as a function of bone activity. Analytic techniques for measuring Pb in blood and urine by graphite furnace atomic absorption and stripping voltametry have been developed and fully validated in our laboratory. Methods have been used clinically and in research for several years and have maintained proficiency in CDC and California state proficiency programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES004850-03
Application #
3253016
Study Section
Safety and Occupational Health Study Section (SOH)
Project Start
1988-09-01
Project End
1991-12-31
Budget Start
1990-09-01
Budget End
1991-12-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Smith, D R; Ilustre, R P; Osterloh, J D (1998) Methodological considerations for the accurate determination of lead in human plasma and serum. Am J Ind Med 33:430-8
Smith, D R; Flegal, A R (1992) Stable isotopic tracers of lead mobilized by DMSA chelation in low lead-exposed rats. Toxicol Appl Pharmacol 116:85-91
Smith, D R; Osterloh, J D; Niemeyer, S et al. (1992) Stable isotope labeling of lead compartments in rats with ultralow lead concentrations. Environ Res 57:190-207
Smith, D R; Niemeyer, S; Flegal, A R (1992) Lead sources to California sea otters: industrial inputs circumvent natural lead biodepletion mechanisms. Environ Res 57:163-74
Osterloh, J D; Sharp, D S; Hata, B (1990) Quality control data for low blood lead concentrations by three methods used in clinical studies. J Anal Toxicol 14:8-11
Osterloh, J D; Selby, J V; Bernard, B P et al. (1989) Body burdens of lead in hypertensive nephropathy. Arch Environ Health 44:304-10